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Progressive Loss of Cerebrovascular Reactivity and Nitric Oxide Bioavailability with Ischemic Stroke in Obese Zucker Rats
Author(s) -
Brooks Steven D,
Branyan Kayla,
DeVallance Evan,
Asano Shinichi,
Hu Hang,
Ren Xuefang,
Rottgen Trey,
Frisbee Jefferson C,
Chantler Paul D
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1275.5
Subject(s) - medicine , stroke (engine) , middle cerebral artery , penumbra , ischemia , perfusion , occlusion , vasodilation , anesthesia , nitric oxide , cardiology , mechanical engineering , engineering
Ischemic stroke occurs when occlusion of a cerebral blood vessel leads to hypoperfusion, ischemia, and infarction of neuronal tissue. In the immediate aftermath of a stroke, maintenance of cerebral blood flow to penumbra is essential to help recover damaged neurons and protect surrounding neurons from insult, and throughout the post‐stroke recovery process, adequate blood flow is necessary to promote recovery and rehabilitation. As such, pre‐existing and stroke‐induced impairments in cerebrovascular reactivity may lead to larger infarcts and worsened long term recovery. The purpose of this study was to evaluate vascular reactivity at 24 hours and 15 days post‐stroke, in the ipsilateral and contralateral hemispheres of rodents with and without comorbid metabolic syndrome. Strokes were induced for 1 hour by transient middle cerebral artery occlusion (tMCAO) in 17 week old lean and obese Zucker rats (LZR, OZR). At either 24 hours post‐occlusion, or 15 days post‐stroke, animals were sacrificed and the ipsilateral (IL) and contralateral (CL) MCAs were removed and cannulated in an ex vivo microvessel preparation. MCA reactivity was assessed in response to acetylcholine. Aortic ring segments were analyzed for nitric oxide (NO) production by DAF assay, and infarct size was measured by TTC stain. In LZR, both IL and CL MCA reactivity at 24 hr. was severely impaired compared to non‐stroke control (over 50% reduction). At 15 days, reactivity decreased another 20% in IL MCA, but remained stable in CL‐MCA. LZR NO bioavailability at 24 hr. was reduced 35% compared to non‐stroke control, which remained constant at 15 days. In OZR, the vascular impairments were more pronounced at 24 hr, and worsened significantly at 15 days. At 24 hr, IL‐MCA reactivity was reduced 80% compared to control, while CL‐MCA was reduced 60%. By 15 days, IL‐MCA reactivity was completely ablated, and CL‐MCA reactivity had decreased another 35%. NO bioavailability for OZR at 24 hr was comparable to LZR stroke, but by 15 days had fallen another 50%. Rates of stroke mortality and infarct size were higher for OZR at both time points as well. These results suggests that ischemic stroke causes severe attenuation of NO bioavailability and cerebrovascular reactivity in both the IL and CL hemispheres of OZR at 24 hrs post‐stroke, with further loss of both at 15 days. While stroke lead to decreased reactivity and NO bioavailability in LZR, degree of impairment was less severe, and remained stable over time. Therefore, the comorbid presence of metabolic syndrome in OZR may increase stroke severity and drive progressive decline of cerebrovascular reactivity following ischemic stroke. Support or Funding Information American Heart Association Predoctoral Fellowship, NIH COBRE grant